内分泌系统 (2).pdf
《内分泌系统 (2).pdf》由会员分享,可在线阅读,更多相关《内分泌系统 (2).pdf(16页珍藏版)》请在得力文库 - 分享文档赚钱的网站上搜索。
1、REVIEWpublished:05 February 2019doi:10.3389/fcvm.2019.00006Frontiers in Cardiovascular Medicine|www.frontiersin.org1February 2019|Volume 6|Article 6Edited by:Dwight A.Towler,University of Texas SouthwesternMedical Center,United StatesReviewed by:Yabing Chen,University of Alabama at Birmingham,United
2、 StatesJoshua D.Hutcheson,Florida International University,United StatesSasha Anna Singh,Harvard Medical School,United StatesAlexander N.Kapustin,AstraZeneca,United Kingdom*Correspondence:Leon J.Schurgersl.schurgersmaastrichtuniversity.nlSpecialty section:This article was submitted toAtherosclerosis
3、 and VascularMedicine,a section of the journalFrontiers in Cardiovascular MedicineReceived:21 September 2018Accepted:14 January 2019Published:05 February 2019Citation:Wasilewski GB,Vervloet MG andSchurgers LJ(2019)TheBoneVasculature Axis:CalciumSupplementation and the Role ofVitamin K.Front.Cardiova
4、sc.Med.6:6.doi:10.3389/fcvm.2019.00006The BoneVasculature Axis:Calcium Supplementation and theRole of Vitamin KGrzegorz B.Wasilewski1,2,Marc G.Vervloet3and Leon J.Schurgers1*1Department of Biochemistry,Cardiovascular Research Institute Maastricht,Maastricht University,Maastricht,Netherlands,2Nattoph
5、arma ASA,Hovik,Norway,3Department of Nephrology and Amsterdam Cardiovascular Sciences,AmsterdamUniversity Medical Centers,Amsterdam,NetherlandsCalciumsupplementsarebroadlyprescribedtotreatosteoporosiseitherasmonotherapyor together with vitamin D to enhance calcium absorption.It is still unclear whet
6、hercalcium supplementation significantly contributes to the reduction of bone fragility andfracture risk.Data suggest that supplementing post-menopausal women with highdoses of calcium has a detrimental impact on cardiovascular morbidity and mortality.Chronic kidney disease(CKD)patients are prone to
7、 vascular calcification in part dueto impaired phosphate excretion.Calcium-based phosphate binders further increaserisk of vascular calcification progression.In both bone and vascular tissue,vitaminK-dependent processes play an important role in calcium homeostasis and it is temptingto speculate tha
8、t vitamin K supplementation might protect from the potentially untowardeffects of calcium supplementation.This review provides an update on current literatureon calcium supplementation among post-menopausal women and CKD patients anddiscusses underlying molecular mechanisms of vascular calcification
9、.We proposetherapeutic strategies with vitamin K2 treatment to prevent or hold progression ofvascular calcification as a consequence of excessive calcium intake.Keywords:calcium paradox,vitamin K,vascular calcification,calcium supplements,bone lossINTRODUCTIONCalcium is an abundant element in nature
10、 and is a major component of sedimentary rockthat covers 75 to 80%of the Earths surface.Calcium is also widely abundant in the humanbody,primarily in bone,and teeth.Calcium salts are occasionally found outside bone in avariety of tissues;this is broadly termed as extra-skeletal calcification.In thes
11、e extra-skeletal sites,calcium exists in multiple forms,including amorphous calcium phosphate,hydroxyapatite,andmagnesium whitlockite.A remarkable observation is that under several pathological conditions,as will be discussed,calcium mineral content of bone declines,while it is increasing onthese ex
12、tra-osseous sites.This has been termed the“calcium paradox”and was introduced todescribe the paradoxical correlation between lower bone calcium content with parallel increasedvascular calcium content(1).The calcium paradox refers to epidemiological data reporting thatpostmenopausal women experience
13、bone loss,yet simultaneously screen positive for vascularcalcification.This phenomenon is common in osteoporotic women and patients suffering fromchronic kidney disease(CKD).Prevalence and morbidity of both cardiovascular disease andosteoporosis are increasing in the global population.Such observati
14、ons have been noted in severalstudies,where a correlation of low bone mineral density(BMD)was associated with increasedcardiovascular mortality(26).Wasilewski et al.Calcium Supplements and Vascular CalcificationThe use of calcium supplements has been widely adviseddue to their assumed ability to sup
15、port bone health and BMD(7,8).Calcium is an essential element for bone growth duringchildhood(9),as well as in preserving bone mineral densityduring adolescence(10).However,a systematic review andmeta-analysis of the effects of calcium supplementation alongwith vitamin D treatment showed that this t
16、reatment was notassociated with a lower incidence of fracture risk in adults,questioning whether calcium supplementation contributes tothe maintenance of healthy bone(11).In turn,recent datasuggest that calcium supplements increase prevalence ofmyocardial infarction(12),and may increase risk of coro
17、naryartery calcification(CAC)(13).Moreover,higher doses ofcalcium from supplements than calcium obtained from dietaryintake might promote cardiovascular calcification(14).Thus,despite the relative benefit of calcium supplementation forbone,calcium supplements became controversial because ofa possibl
18、y increased cardiovascular risk.Substantially differentfrom calcium from dietary sources,calcium form supplementsinduce an acute rise in serum calcium levels that highly oscillatesin blood for up to 6h(15,16).The plasma calcium concentrationis tightly regulated by vitamin D,parathyroid hormone(PTH),
19、and calcitonin(17,18).VitaminK-dependentproteins(VKDP)alsoplayanimportant role regulating mineralization both in bone andthe vasculature.Osteocalcin(OC)is produced exclusivelyby osteoblasts and supports the binding of calcium to thebone mineral matrix,whereas matrix Gla-protein(MGP)issynthesized by
20、vascular smooth muscle cells and chondrocytesto prevent ectopic calcification.While hepatically producedcoagulation factors are the prototypical VKDP,the extra-hepaticVKDP also unequivocally need vitamin K as cofactor to becomebiologically active.Related to that,vitamin K2 has been shownto prevent b
21、one loss and strength and prevents stiffening ofarteries(19,20).Western diet does not provide sufficient vitaminK to activate all OC and MGP that is produced(21,22).Alsoin CKD patients,vitamin K deficiency is prevalent,so K2supplementation has been suggested as treatment option toattenuate vascular
22、calcification(23,24).In this review we provide the latest insights of the calciumparadox and the potential of using vitamin K to support bothbone and vascular health.BONE METABOLISMCalcification generally is a physiological process,necessaryto build bone and dentin.Bone provides structural support,s
23、trength,necessary for locomotion,and protection from theenvironment.The balance in bone formation and boneresorption is crucial for optimal bone health.A disturbed balanceof this process results in bone loss and is termed osteoporosis.Duringchildhoodboneisformedandbonepeakmassisachievedduring young
24、adulthood,after which bone mass graduallydeclines.Bone loss is the consequence of bone resorptionoutbalancing bone formation(25).This is accompanied bybone architectural changes including trabecular bone becomingthinner,less abundant,and osteoclastic perforation of corticalbone(26).Bone FormationThe
25、 skeleton is systematically renewed in the process of boneremodeling to maintain strength and rigidity.Bone remodelingcan be considered to be part of calcium homeostasis systemand enables the skeleton to adapt to changes.Bones adapt theirstructure depending on their function,mechanical strain andnee
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- 内分泌系统 2
限制150内